The interactions and mechanism by which dimethybenzanthracene (DMBA) causes mammary carcinoma will be examined by a technique which involves the implantation of DMBA directly on the mammary gland of the rat. This method of local tumor induction results in the production of cancers at predictable sites, and hence provides a model system for the analysis of preneoplasia in the mammary gland. The method will permit the determination of the critical period for cancer induction and establish the appropriate time periods for further examination of the biochemical and cellular responses that are correlated with cancer induction. The interactions of various steroid hormones, especially estrogens and progestagens, with DMBA and the binding of H3-DMBA to cellular components will be assessed during the critical period. In addition, estrogen receptor binding and hormone induced responses will be studied during the preneoplastic and neoplastic periods. These binding and response patterns will be compared to those observed in the non-cancerous tissue. This proposal is designed to define the important biochemical and cellular events that are taking place during cancer induction and to establish the relationships between steroid hormone receptor binding and steroid induced responses in normal and abnormal mammary tissue.